On May 26, 2021 AIM ImmunoTech Inc. (NYSE American: AIM) reported that it has completed dosing of Cohort 3 in a Phase 1 clinical study to assess the safety, tolerability and biological activity of Ampligen as an intranasal therapy, reporting no serious adverse events (Press release, AIM ImmunoTech, MAY 26, 2021, View Source [SID1234580606]).

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This is consistent with results in the first two cohorts of the study and at escalating doses.The study protocol called for a total of 40 healthy subjects to receive repeated administration of either Ampligen or a placebo. Subjects in Cohort 1 received 75 μg of Ampligen, subjects in Cohort 2 received 200 μg of Ampligen and subjects in Cohort 3 received 500 μg. The study is already proceeding with Cohort 4, with subjects receiving 1250 μg.

The Centre for Human Drug Research (CHDR), an independent institute located in Leiden in the Netherlands, is conducting the Phase 1 clinical study AMP-COV-100 (CHDR2049), titled "A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Activity of Repeated Intranasal Administration of Ampligen (Poly I:Poly C12U) in Healthy Subjects." AIM is sponsoring and funding the clinical study.

On May 26, 2021 Veracyte, Inc., (Nasdaq: VCYT) reported new data that show the company’s Afirma Xpression Atlas (XA) can identify clinically relevant gene fusions in thyroid nodule samples collected via fine needle aspiration (FNA) (Press release, Veracyte, MAY 26, 2021, View Source [SID1234580622]). The findings, which will be presented June 4 at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, support use of the whole transcriptome RNA-sequencing test to detect gene fusions that may guide the use of targeted treatments for thyroid cancer.

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"The increasing availability of targeted therapies for thyroid cancer, including tyrosine kinase inhibitors, means physicians must have tools that reliably identify the patients who may benefit from these therapies," said Lori J. Wirth, M.D., medical director of the Center for Head and Neck Cancers, Mass General Cancer Center, who will present the data. "Using the Afirma XA test, we were able to identify and report the prevalence of clinically relevant gene variants and fusions in real-world thyroid nodule samples."

The American Cancer Society predicts that more than 44,000 individuals will be diagnosed with thyroid cancer in the United States this year. Pathologists use the Bethesda system to classify thyroid nodules into several categories – from benign to malignant – using FNA samples. The Afirma XA uses whole transcriptome RNA sequencing to identify 905 DNA variants and 235 RNA fusions in 593 genes on FNAs taken from thyroid nodules. Increasing numbers of these gene fusions can be targeted by small-molecule therapies.

In the study to be presented at ASCO (Free ASCO Whitepaper) (Abstract 6803), researchers analyzed data from 50,644 thyroid FNA samples submitted to Veracyte’s CLIA laboratory to determine the prevalence of selected receptor tyrosine kinase (RTK) fusions of ALK, BRAF, NTRK1/3 or RET fusions. The Afirma Genomic Sequencing Classifier (GSC) had been used to classify samples as benign or suspicious following an indeterminate result by cytopathology (Bethesda III-IV). Researchers performed the Afirma XA on samples that were deemed suspicious by the GSC or that were likely or confirmed cancerous by cytopathology (Bethesda V/VI).

More than 32,000 samples were classified as benign with the Afirma GSC and no RTK fusions were identified. Of the 16,594 samples classified as suspicious by the Afirma GSC, 3% harbored RTK fusions. In the nearly 1,700 samples classified as either suspicious for malignancy or malignant, 8% were found to have RTK fusions. The most common fusion was ETV6/NTRK3, while BRAF fusions had the most diversity with 80 different gene partners.

"These findings suggest that by using the Afirma GSC and XA tests, physicians can confidently classify individual patients’ thyroid nodules and, for nodules that are malignant, determine whether treatment with a targeted therapy is appropriate," said Richard T. Kloos, M.D., Veracyte’s executive medical director. "We look forward to future analyses of how Afirma XA test results impact initial treatment and patient outcomes."

On May 26, 2021 Engine Biosciences ("Engine") reported the successful completion of an oversubscribed $43 million Series A funding round (Press release, Engine Biosciences, MAY 26, 2021, View Source [SID1234580638]). Engine identifies errors in the complex genetic codes of diseases, fixing them with precise therapeutic solutions. This round was led by Polaris Partners and also included new investors Invus and one of the world’s premier institutional investors, based in Singapore. Existing investors also participated in the Series A, which included 6 Dimensions Capital, WuXi AppTec, DHVC, EDBI, Baidu Ventures, Vectr Ventures, Goodman Capital, WI Harper, and Nest.Bio. Amy Schulman, Managing Partner at Polaris Partners, has joined the Engine Biosciences Board of Directors. Engine has now raised $53 million to date, including $10 million in a 2018 seed round.

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"The past year has reinforced the importance of rapid innovation and adaptation"

Located in Singapore and Silicon Valley, Engine has been operating at the intersection of data science, machine learning, high-throughput biology experimentation, combinatorial genetics, chemistry, and drug discovery. Engine’s technologies enable researchers and drug developers to uncover the gene interactions and biological networks underlying diseases orders-of-magnitude faster and more cost-effectively than conventional methods. Additionally, the company generates important insights for precision medicine applications.

"Many breakthrough tools to edit, program, and modulate biology have emerged and matured in recent years. The fundamental question continues to be whether we know the disease-driving errors in the genetic code of biology to direct these tools, including therapeutics," said Jeffrey Lu, Engine Biosciences’ Co-Founder and CEO. "We are honored that this preeminent group of life science and technology investors has recognized the progress our team has made and is supporting our mission to unleash new medicines by deciphering biology."

Engine has already been progressing its novel biology findings into drug discovery programs and proprietary small molecule inhibitors. It will utilize the new funds to expand its portfolio of precision oncology therapeutics, prepare for its first clinical programs, and scale its proprietary technology platform.

"The past year has reinforced the importance of rapid innovation and adaptation," said Polaris Partners’ Amy Schulman. "Engine’s distinct combination of biology, technology, and drug discovery, as well as its global perspective, may well enable the company to be particularly capable of realizing the promise of artificial intelligence in drug discovery and tackling a wide variety of diseases. We are excited to be part of this next step with the team."

Initial Disease Targets

Engine has performed several large-scale computational and experimental cycles with respect to genetic interactions and their relevance to multiple cancers, yielding new and subsequently validated discoveries. Engine’s growing and advancing pipeline of targeted therapies for genetically-defined patient populations has shown promise in treating liver, ovarian, colorectal, and breast cancers, representing major areas of unmet medical need and, in total, approximately 2.5 million deaths every year.

Through collaborations, Engine has also demonstrated its platform’s applicability in other disease areas and will continue to enable new therapeutics for more patients.

"We believe Engine’s AI-enabled technology platform has the potential to discover new biology targets and disease-causing links amongst known targets," said Leon Chen, CEO and Founding Partner of 6 Dimensions Capital. "Considering the field’s tremendous needs for the right drug targets for the right patients and Engine’s unique capabilities in finding those, we continue to be excited by Engine’s potential to power new medicines."

How It Works: NetMAPPR and CombiGEM

Two scientific innovations lie at the heart of Engine Biosciences: NetMAPPR and CombiGEM. NetMAPPR is Engine’s searchable biology platform, revealing gene combinations and drug targets integral to diseases. Employing combinatorial CRISPR, CombiGEM enables experimental confirmation of how genes and gene combinations relate to disease in supercharged fashion.

Engine has engineered NetMAPPR to operate in predict-test-learn cycles and scale for many research and drug discovery programs. Advanced computational tools leverage large patient and disease datasets and analyze the vast universe of millions-to-billions of gene interactions, making predictions on the most critical biologies for medicines. Engine uses its patented CombiGEM technology to test hundreds of thousands of gene interactions experimentally in diseased cells, thus breaking through bottlenecks in validation and data generation. The resulting data from well-controlled experiments improves Engine’s machine learning algorithms, while high-ranking genes are prioritized for drug discovery and development.

Compared to conventional approaches that are challenged by human limitations and less efficient and less precise experimental systems and hence cover tiny slices of biology, NetMAPPR searches much wider expanses of the complex architecture of biology at greater speeds, unleashing more new therapeutic opportunities.

On May 26, 2021 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, and Addario Lung Cancer Medical Institute (ALCMI) reported they will present on the progress of "Biomarker Analysis in High PD-L1 Expressing NSCLC Patients Treated With PD-1/PD-L1 Based Therapy With or Without the Addition of Platinum Based Chemotherapy (BEACON-Lung) (Press release, Biodesix, MAY 26, 2021, View Source [SID1234580654])." The BEACON-Lung study aims to evaluate biomarkers to predict overall survival and early progression outcomes in treatment-naïve advanced stage non-small cell lung cancer (NSCLC) patients with high PD-L1 expression. The first patient participant enrolled in the study this week.

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"The BEACON-Lung study furthers ALCMI’s mission to work with partners like Biodesix to overcome barriers to treatment in lung cancer," said Tony Addario, chair and CEO of ALCMI. "This study will enable us to develop a better understanding of how biomarkers can unlock treatment options for patients with NSCLC and improve survivorship."

The study, being conducted through ALCMI’s prestigious research consortium of leading US academic centers, launched early this year. Nearly half of the targeted 10 sites are actively enrolling with a target enrollment of 390 patients. BEACON-Lung will use Biodesix’s Primary Immune Response (PIR) test to classify patients receiving PD-1/PD-L1 therapy or PD-1/PD-L1 plus carboplatin-based chemotherapy and identify those who may benefit from more aggressive treatment regimens.

"As an oncologist, I am excited by the progress we have made for patients who are now diagnosed with non-small cell lung cancer," said Dr. Mary Jo Fidler, principal investigator for the BEACON trial and associate professor in the Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy at Rush Medical College. "However, to identify the best treatment course for an individual patient still requires the development of biomarkers, especially in the field of immunotherapy. BEACON-Lung is a study that aims address this current gap in biomarker development and treatment selection for advanced non-small cell lung cancer."

The BEACON-Lung study is designed to generate key data to further the development of immunotherapy biomarkers for treatment naïve NSCLC patients. Currently, PDL1 expression is the only clinically validated biomarker predicting patient response to front line PD-1/L1 directed immunotherapy. However, PD-L1 expression remains an imperfect marker, and this study will also help determine if patients should pursue other treatment regimens.

"We are thrilled that the BEACON-Lung study is now launched," said Dr. James Jett, CMO of Biodesix. "This study will allow us to evaluate performance of Biodesix’s PIR test in the treatment naïve NSCLC patient population receiving immunotherapy. We are committed to the advancement of biomarker research and to fulfill an unmet need in the NSCLC treatment landscape."

Presentation Title: Biomarker Analysis in High PD-L1 Expressing NSCLC Patients Treated With PD-1/PD-L1 Based Therapy With or Without the Addition of Platinum Based Chemotherapy (BEACON-Lung)
Authors: Mary J. Fidler, Victoria Meucci Villaflor, Amol Rao, Balazs Halmos, Erin Marie Bertino, Raymond U. Osarogiagbon, David Paul Carbone; Rush University Medical Center, Chicago, IL; Northwestern University Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Memorial Care, Laguna Hills, CA; Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY; The Ohio State University Comprehensive Cancer Center, Columbus, OH; Baptist Cancer Center, Multidisciplinary Thoracic Oncology Department, Memphis, TN
Abstract Number: TPS9126
Session Date/Time: June 4, 2021 / After 9am E.T.

About ALCMI
The Addario Lung Cancer Medical Institute (ALCMI, voiced as "Alchemy"), founded in 2008 as a 501c(3) non-profit organization by lung cancer survivor Bonnie J Addario, is a patient-centric, international research consortium driving research otherwise not possible. Working in tandem with its "partner" foundation, GO2 Foundation for Lung Cancer, ALCMI powers collaborative initiatives in genetic (molecular) testing, therapeutic discoveries, targeted treatments, and early detection. ALCMI combines scientific expertise found at its network of 26 member academic institutions through its network of community cancer centers to accelerate patient access to research.

On May 26, 2021 Cleveland Clinic researchers reported that they have identified a promising drug target for treating and preventing aggressive, drug-resistant prostate cancer (Press release, Cleveland Clinic Foundation, MAY 26, 2021, View Source [SID1234583288]).

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Nima Sharifi, M.D.

The team, led by Nima Sharifi, M.D., of Cleveland Clinic’s Lerner Research Institute, demonstrated that inhibiting the protein H6PD led to significantly reduced tumor sizes and improved survival among mouse models with drug-resistant prostate cancer. The H6PD levels also were elevated in biopsied patient tumors, suggesting the protein might be targeted in patients for treatment.

"New treatment approaches for drug-resistant prostate cancer are desperately needed," said Dr. Sharifi, director of Cleveland Clinic’s Genitourinary Malignancies Research Center. "These findings suggest an entirely new strategy for treatment of men with this aggressive form of prostate cancer."

Enzalutamide, a current standard-of-care hormone therapy for metastatic prostate cancer, works by blocking androgen receptors, which are proteins that help drive cancer cells. While initially effective, most patients eventually develop resistance to the treatment. This resistance occurs when androgen receptors are blocked and cancer cells adapt to get their "fuel" from a similar receptor, called the glucocorticoid receptor.

These glucocorticoid receptors bind to and interact with the stress hormone cortisol. In an earlier study published in eLife, Dr. Sharifi and his team linked enzalutamide resistance to increased tumor cortisol levels. They found that tumors typically express a protein called 11β-HSD2, which inactivates cortisol. However, when this protein expression is inhibited in some tumors, cortisol and the glucocorticoid receptor are stimulated and become available for use by cancer cells.

"Taken together, our study findings suggest that pharmacologically inhibiting the H6PD protein can reverse drug resistance in prostate cancer cells," said Dr. Sharifi. "By blocking this protein, we are able to prevent cancer cells from utilizing their backup fuel supply – cortisol and its receptor. When we block this pathway, tumors begin to become responsive to standard treatments again."

In this new study, the researchers demonstrated that, in addition to decreased expression of 11β-HSD2, resistant tumors also have increased H6PD levels.

"With lower levels of 11β-HSD2, which normally functions to cut off the fuel supply to drug-resistant cancer cells, the cells are free to continue to grow and spread unchecked," said Dr. Sharifi. "By inhibiting the H6PD protein, however, we were able to reinstate anti-cortisol effects. This finding is key to better understanding how disruptions in cortisol metabolism contribute to cancer cells’ growth and spread."

Dr. Sharifi’s clinical collaborator Eric Klein, M.D., chair of Cleveland Clinic’s Urology & Kidney Institute and a co-author on the study, said, "We found elevated levels of H6PD in both animal models and patient tissues, particularly after treating tumors with enzalutamide. These findings hold promise for novel precision medicine approaches in the management of men with aggressive prostate cancer."

The researchers targeted H6PD with rucaparib, a drug already approved by the U.S. Food and Drug Administration. Dr. Sharifi collaborated with scientists from Cleveland Clinic’s Center for Therapeutics Discovery to identify what parts of rucaparib are chemically necessary to inhibit the protein.

Researchers administered enzalutamide to mouse models of aggressive prostate cancer that expressed H6PD and those where the protein was blocked with rucaparib. The models where H6PD was blocked had significantly smaller tumors and longer progression-free survival following enzalutamide treatment.

Jianneng Li, PhD, a post-doctoral fellow in Dr. Sharifi’s lab, is first author on the study, which was supported by the National Cancer Institute and the Prostate Cancer Foundation.

"These findings represent an exciting new opportunity to potentially reverse drug resistance in advanced prostate cancer," said Howard R. Soule, PhD, Executive Vice President and Chief Science Officer of the Prostate Cancer Foundation. "PCF commends Dr. Sharifi and the team on their achievement and proudly supports their work to bring us closer to our mission to eliminate death and suffering from prostate cancer."